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  • 1
    Electronic Resource
    Electronic Resource
    Human liver budesonide sulphotransferase is inhibited by testosterone and correlates with by testosterone sulphotransferase (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 49-54 
    Details
    ISSN: 1432-1041
    Keywords: Budesonide ; liver ; man ; sulphotransferase ; testosterone ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Budesonide, a corticosteroid used in the treatment of asthma and allergic reactions, is almost entirely cleared by metabolism in man. We describe the sulphation of budesonide in human liver and lung and provide evidences that the sulphation of budesonide is catalysed by testosterone sulphotransferase. A rapid and reproducible radiometric assay for budesonide sulphotransferase is described. Liver specimens were obtained from 35 men and 65 women and lung specimens from 2 women and 17 men. The average hepatic budesonide sulphation rate was significantly higher in men (41.1 pmol·min−1·ml−1) than women (28.2 pmol·min−1·mg−1). In the lung, the mean budesonide sulphation rate was 5.0 pmol·min−1·mg−1. Testosterone strongly inhibited the hepatic sulphation of budesonide, whereas p-nitrophenol and dopamine were poor inhibitors; the IC50 was 7.0 uM (testosterone), 320 uM (p-nitrophenol) and 510 uM (dopamine). The hepatic rates of testosterone, p-nitrophenol and dopamine sulphation were measured in the same samples assayed for budesonide sulphotransferase. There was a correlation between the hepatic rates of budesonide and testosterone sulphation (P〈0.001; r=0.810). The activity of testosterone sulphotransferase was significantly greater in men than women (22.0 vs. 17.2 pmol·min−1·mg−1), wheres those of dopamine and p-nitrophenol sulphotransferase were not sex dependent. The hepatic activity of budesonide sulphotransferase parallels that of testosterone suggesting that sulphation is an important reaction in the metabolism of budesonide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195915
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  • 2
    Electronic Resource
    Electronic Resource
    Eosinophil locomotion and the release of IL-3 and IL-5 by allergen-stimulated mononuclear cells are effectively downregulated in vitro by budesonide (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 26 (1996), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Treatment of aliergic asthma with inhaled corticosteroids, such as budesonide (BDN), results in downregulation of T-cell activation and of eosinophil recruitment.Objective Since blood concentrations of BDN, although significantly lower than those measured in the lung, may still have anti-inflammatory effects, we evaluated the activity of BDN in vitro on: allergen-induced release of lymphokines involved in eosinophil chemotaxis (i.e. IL-3 and IL-5), at drug concentrations similar to those obtained in vivo in the lung (10−8 M), and eosinophil locomotion, at ‘systemic concentrations’ of the drug (10−10 M and 10−9M).Methods Twenty-three atopic asthmatic subjects (atopics) sensitized to Dermatophagoides pteronyssinus (Dp) and seven non-atopic healthy subjects (controls) were studied. Purified blood mononuclear cells (BMC) were stimulated with Dp, with or without BDN 10−8 M and, after 6 days, the supernatants were collected and frozen to test their ehemotactie activity toward purified blood eosinophils and their levels of interleukin (IL)-3 and IL-5 by immunoassay. BMC were then pulsed for additional 18h with [3H]thymidine to evaluate allergen-induced T-cell proliferation. In addition, to test possible direct effects of ‘systemic concentrations’ of the drug on eosinophil locomotion, blood eosinophils were incubated for 1 h with BDN (10−10 M and 10−9 M) prior to test their ehemotactie response toward recombinant human IL-3 and IL-5.Results Stimulation of BMC from atopies with Dp induced a statistically significant increase in [H]thymidine incorporation (P 〈 0.05); secretion of ehemotactie factors for eosinophils (P 〈 0.001) and the release of IL-3 and IL-5 (P 〈 0.005 and P 〈 0.05 respectively). BDN, at the concentration of 10−8 M, was able to significantly down-regulate T-cell proliferation (P 〈 0.05), the secretion of ehemotactie factors for eosinophils (P 〈 0.001) and the release of IL-3 and IL-5 (P 〈 0.01 and P 〈 0.05 respectively). Similarly, “systemic concentrations” of BDN (10−10 M and 10−9 M) totally inhibited the ehemotactie response of blood eosinophils toward recombinant human IL-3 and IL-5 (P 〈 0.005).Conclusions Concentrations of BDN similar to those obtained in vivo are effective in inhibiting both the release of eosinophils chemotaxins by allergen-activated mononuclear cells and eosinophil locomotion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1996.tb00592.x
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of “systemic” budesonide concentrations on in vitro allergen-induced activation of blood mononuclear cells isolated from asthmatic patients (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 50 (1995), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Blood levels of inhaled corticosteroids are significantly lower than those measured in the lung, but their concentration could still have anti-inflammatory effects. To determine whether budesonide, at concentrations similar to those obtained in blood after drug inhalation (10 −9 M), could downregulate the allergen-induced activation of mononuclear cells, we studied 21 atopic patients, sensitized to Dermatophagoides pteronyssinus (Der p). On blood mononuclear cells, isolated from these patients, incubated with Der p allergen extract and with or without budesonide, we evaluated: 1) the proliferative response of T cells; 2) the expression of two surface activation markers, the HLA-DR antigens and the interleukin (IL)-2 receptors; and 3) the release of cytokines known to modulate the allergic processes. Allergen-induced T-cell proliferation was associated with increased HLA-DR antigen and IL-2 receptor expression (P 〈 0.001), and with increased release of IL-2, interferon-gamma (IFN-γ), IL-1β, tumor necrosis factor-alpha (TNF-α), and granulocyte/macrophage colony-stimulating factor (GM-CSF). The addition of budesonide at the beginning of the cell cultures induced a dose-dependent inhibition of T-cell proliferation, still significant (P 〈 0.05) at the lowest concentrations tested (10 −9 and 10−10 M). A significant inhibitory effect on T-cell proliferation was also present when budesonide (10 −9 M) was added to the cell cultures 3 or 5 days after the beginning of the cell cultures. In addition, budesonide 10−9 M significantly decreased the expression of IL-2 receptors (P 〈 0.05), but not of HLA-DR antigens, and significantly reduced the release of IL-1β and GM-CSF (JP 〈 0.05), but not of IL-2, IFN-γ, and TNF-α. Thus, the blood concentrations of budesonide, after drug inhalation, may exert some anti-inflammatory effect, downregulating both “local” (through the bronchial circulation) and “systemic” allergen-specific immune reactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1995.tb01169.x
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  • 4
    Electronic Resource
    Electronic Resource
    Budesonide Down-Regulates Eosinophil Locomotion But Has No Effects on ECP Release or on H2O2 Production (1999)
    Springer
    Lung 177 (1999), S. 219-228 
    Details
    ISSN: 1432-1750
    Keywords: Key words: Allergic asthma—T-lymphocytes—Cytokines—Granulocytes—Chemotaxis—Interleukin-5—Corticosteroids.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Treatment of allergic asthma with inhaled corticosteroids results in local down-regulation of proinflammatory cytokine synthesis and in marked decrease in tissue eosinophilia. Blood concentrations of inhaled corticosteroids, although significantly lower than those measured in the lung, may still have antiinflammatory effects on circulating eosinophils, reducing their ability to migrate. The aim of our study was to evaluate in vitro the activity of budesonide on blood eosinophils by measuring their chemotactic response, eosinophil cationic protein (ECP) release, and hydrogen peroxide (H2O2) production in the presence of different drug concentrations similar to those obtained at airway level (10−8 and 10−7 M) and at blood level (10−10 and 10−9 M). Partially purified blood eosinophils, isolated from 23 asthmatic subjects, were used to evaluate the activity of budesonide on: (1) chemotaxis toward the activated fifth component of complement (C5a, 0.1 μg/ml) or recombinant human (rh) interleukin (IL)-5 (200 pg/ml), (2) ECP release by cells stimulated with tetradecanoylphorbol acetate (TPA) and (3) H2O2 production by TPA-activated cells. The chemotactic response to C5a was down-regulated significantly by budesonide only by the highest concentrations tested (10−8 and 10−7 M); differently, budesonide was effective in inhibiting eosinophil migration toward rhIL-5, at all concentrations tested (p 〈 0.01, each comparison). By contrast, no drug-induced modifications were observed in ECP release or in H2O2 production (p 〉 0.05, each comparison). We conclude that concentrations of budesonide similar to those obtained in vivo are effective in inhibiting eosinophil locomotion but not in down-regulating the release of reactive oxygen species and granule-associated proteins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007642
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  • 5
    Electronic Resource
    Electronic Resource
    Treatment of chronic sporadic-type non-A, non-B hepatitis with lymphoblastoid interferon: Gamma GT levels predictive for response (1994)
    Springer
    Digestive diseases and sciences 39 (1994), S. 866-870 
    Details
    ISSN: 1573-2568
    Keywords: non-A, non-B hepatitis ; chronic hepatitis ; interferon ; hepatitis C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon-α treatment in chronic sporadic-type non-A, non-B hepatitis. We also aimed to determine if histological or liver function data could predict either response or relapse. Sixty patients with chronic sporadic-type non-A, non-B hepatitis were randomized in two groups of 30. One group was treated with interferon-α (3 MU thrice weekly) for one year; the other group was untreated controls. The treated group was followed for another year after interferon withdrawal. Liver function tests were performed during treatment. Liver biopsy was carried out before and a year after randomization. We evaluated rate of response [normalization of alanine aminotransferase (ALT) levels for at least three consecutive months] and rate of relapse (ALT rebound after therapy suspension). We also looked at possible predictive factors for response and relapse. In the treatment group the rate of response was 55% (16/29). No control patient exhibited ALT normalization. Among the responders, 31% (5/16) relapsed after interferon withdrawal. Low gamma GT and female sex are positive predictive factors of response (P〈0.01 andP〈0.02 respectively). Presence of portal and periportal inflammation at the second liver biopsy was correlated with relapse (P〈0.05). In conclusion, human lyphoblastoid interferon-α treatment for one year is beneficial in patients suffering from chronic sporadic-type non-A, non-B hepatitis. Low pretreatment gamma GT levels and female sex are positive predictors of response in this patient population. Low degrees of portal and periportal inflammation, posttreatment, predict maintenance of response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02087435
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